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Review
, 47 (1), 351-356

Initiating DNA Replication: A Matter of Prime Importance

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Review

Initiating DNA Replication: A Matter of Prime Importance

Stephen D Bell. Biochem Soc Trans.

Abstract

It has been known for decades that the principal replicative DNA polymerases that effect genome replication are incapable of starting DNA synthesis de novo Rather, they require a 3'-OH group from which to extend a DNA chain. Cellular DNA replication systems exploit a dedicated, limited processivity RNA polymerase, termed primase, that synthesizes a short oligoribonucleotide primer which is then extended by a DNA polymerase. Thus, primases can initiate synthesis, proceed with primer elongation for a short distance then transfer the primer to a DNA polymerase. Despite these well-established properties, the mechanistic basis of these dynamic behaviours has only recently been established. In the following, the author will describe recent insights from studies of the related eukaryotic and archaeal DNA primases. Significantly, the general conclusions from these studies likely extend to a broad class of extrachromosomal element-associated primases as well as the human primase-related DNA repair enzyme, PrimPol.

Keywords: DNA replication; archaea; primase.

Conflict of interest statement

The Author declares that there are no competing interests associated with this manuscript.

Figures

Figure 1.
Figure 1.. Model for how the bacterial RNA polymerase initiates RNA synthesis.
The initiating nucleotide is stabilized by base pairing with the corresponding template base, partial base stacking with the preceding template base and coordination of the 5′-triphosphate with highly conserved residues in the polymerase active site. The consequence is that the nucleotide is positioned in a position analogous to the 3′-base of an elongating RNA chain. See reference [14] for further details.
Figure 2.
Figure 2.. Two nucleotide-binding sites in the Sulfolobus primase.
(A) Structure of S. solfataricus PriSLX assembly. PriS is in yellow and contains the polymerization elongation site, PriL is in wheat and PriX, which possesses the binding site for the initiating nucleotide triphosphate, is in pink. The ATP analog AMPCPP is shown in pale blue with atoms represented as spheres. (B) A close-up view of the initiation site in PriX — residues important for binding the triphosphate group of the pale blue AMPCPP directly or via a co-ordinated manganese ion (grey sphere) are shown in dark blue. See reference [13] for details. The figure was prepared using PDB File 5OF3.
Figure 3.
Figure 3.. A comparison of the helical bundle regions of PriX, human PriL, ORF904 and RepB’.
The initiating nucleotide bound to PriX is shown in pale blue. The figure was prepared from the co-ordinates in PDB files 5OF3, 5FOQ, 3MIM and 3H20.

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References

    1. Barry E.R. and Bell S.D. (2006) DNA replication in the archaea. Microbiol. Mol. Biol. Rev. 70, 876–887 10.1128/MMBR.00029-06 - DOI - PMC - PubMed
    1. Aravind L., Leipe D.D. and Koonin E.V. (1998) Toprim — a conserved catalytic domain in type IA and II topoisomerases, DnaG-type primases, OLD family nucleases and RecR proteins. Nucleic Acids Res. 26, 4205–4213 10.1093/nar/26.18.4205 - DOI - PMC - PubMed
    1. Hou L., Klug G. and Evguenieva-Hackenberg E. (2014) Archaeal DnaG contains a conserved N-terminal RNA-binding domain and enables tailing of rRNA by the exosome. Nucleic Acids Res. 42, 12691–12706 10.1093/nar/gku969 - DOI - PMC - PubMed
    1. Lao-Sirieix S.H., Pellegrini L. and Bell S.D. (2005) The promiscuous primase. Trends Genet. 21, 568–572 10.1016/j.tig.2005.07.010 - DOI - PubMed
    1. Pellegrini L. (2012) The Pol alpha-primase complex. Subcell. Biochem. 62, 157–169 10.1007/978-94-007-4572-8_9 - DOI - PubMed

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